Steatosis/f Fibrosis/c Liver Name Hepatomegaly Elevated transaminases ALF Cholestasis atty liver irrhosis tumor Other Diagnostic markers Specific treatment Representative references (PMID or DOI) DISORDERS OF NITROGEN-CONTAINING COMPOUNDS Disorders of ammonia detoxification Protein restriction, ammonia scavengers N-acetylglutamate synthase deficiency X Ammonia (B), Urea (P), Amino acids (P) (carglumic acid), citrulline 28900784, 11131349 Protein restriction, ammonia Carbamoylphosphate synthetase I deficiency X X X X Ammonia (B), ASAT/ALAT (P), Urea (P), Amino acids (P) scavengers, citrulline, liver transplant 28900784 Ammonia (B), ASAT/ALAT (P), Urea (P), Amino acids (P), Protein restriction, ammonia 28900784, 22129577, 24485820, 21884343, Ornithine transcarbamylase deficiency X X X X X HCC Orotic acid (U) scavengers, citrulline, liver transplant 27070778, 24485820, 28887792 Ammonia (B), ASAT/ALAT (P), Urea (P), Amino acids (P), Protein restriction, ammonia Argininosuccinate synthetase deficiency X X X X HCC Orotic acid (U) scavengers, arginine, liver transplant 28900784, 29209134, 15334737 Ammonia (B), ASAT/ALAT (P), Urea (P), Amino acids (P, U), Protein restriction, ammonia Argininosuccinate lyase deficiency X X X X HCC Orotic acid (U) scavengers, arginine, liver transplant 28900784 Ammonia (B), ASAT/ALAT (P), Urea (P), Amino acids (P), Arginase deficiency X X X X X HCC Orotic acid (U) Protein restriction, ammonia scavengers 28900784, 22964440 Ammonia (B), ASAT/ALAT (P), Urea (P), Amino acids (P, U), Protein restriction, ammonia Mitochondrial ornithine transporter deficiency X X X X X Orotic acid (U) scavengers, citrulline 28900784 MCT oil, lactose-free formula, fat- Ammonia (B), ASAT/ALAT (P), Urea (P), Amino acids (P), soluble vitamins, arginine, sodium Citrin deficiency X X X X HCC Orotic acid (U), Galactose (RBC) pyruvate 28900784, 30591617, 18385606, 14606711 Disorders of amino acid transport Protein restriction, ammonia Lysinuric protein intolerance X X X X Ammonia (B), Amino acids (P, U) scavengers, citrulline 28057010 Disorders of tyrosine metabolism Hawkinsinuria X Organic acids (U) 10412819 AST/ALT (P), Amino acids (P), Organic acids (U), Tyrosine restriction, NTBC, liver Tyrosinemia type I X X X X X HCC Succinylacetone (P, U), AFP (S) transplant 6188953 Disorders of sulfur amino acid and sulfide metabolism AST/ALT (P), Amino acids (P), Homocysteine (P), SAH/SAM Glycine N-methyltransferase deficiency X X (P) 11596649, 14739680 AST/ALT (P), CK (P), Coagulation factors (P), Amino acids (P), Methionine restriction, creatine, S-adenosylhomocysteine hydrolase deficiency X HCC Homocysteine (P), SAH/SAM (P) phosphatidylcholine, liver transplant 26527160, 26095522 AST/ALT (P), Glucose (S), Amino acids (P), Purines (U), Adenosine kinase deficiency X X X X Total/direct bilirubin (S) Methionine restriction 26642971 Disorders of branched-chain amino acid metabolism AST/ALT (P), NH3 (P), Amino acids (P), Organic acids (U), Protein restriction?, carnitine Dihydrolipoamide dehydrogenase deficiency X X Acylcarnitines (DBS, P), Lactate (P) supplementation 9161958, 9764998, 23478190 AST/ALT (P), NH3 (P), Glucose (S), Organic acids (U), Protein restriction, carnitine 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency X X X Acylcarnitines (DBS, P), Lactate (P) supplementation 2443756, 9658458, 11593134, 27284350 Methylmalonate semialdehyde dehydrogenase deficiency X X AST/ALT (P), Organic acids (U), Lactate (P) DOI:10.32598/jpr.7.1.55, 21863277 Propionic acidemia X Amino acids (P), Organic acids (U), Acylcarnitines (DBS, P) Low protein diet, carnitine 29433791 Methylmalonic aciduria due to methylmalonyl-CoA mutase Amino acids (P), Organic acids (U), MMA (S), Acylcarnitines Low protein diet, carnitine, deficiency X X (DBS, P) hydroxycobalamin 29433791 Combined malonic and methylmalonic aciduria X X Organic acids (U), MMA (S) 21841779, 26915364 Disorders of proline and ornithine metabolism Prolidase deficiency X X Amino acids (U) 27385964, 16470701 DISORDERS OF VITAMINS, COFACTORS, METALS AND MINERALS Disorders of cobalamin metabolism Homocysteine, total (P), B12 (S), Blood count, Organic acids cblC disease X X X (U), Acylcarnitines (DBS, P), Amino acids (P) Hydroxycobalamin, betaine 30178268 Disorders of riboflavin metabolism AST/ALT (P), CK (P), Glucose (S), Amino acids (P), Organic Multiple acyl-CoA dehydrogenase deficiency type 1 X X acids (U), Acylcarnitines (DBS, P) 10052728, 7173260 Disorder of pyridoxine metabolism PNPO deficiency X X 5HIAA/HVA/3OMD (CSF), Amino acids (P) PLP 25256445, 26108646 Disorders of copper metabolism Wilson disease X X X X X HCC, ICC Copper (S, U), Ceruloplasmin (S), ASAT/ALAT (P), Blood count Zinc, penicillamine, trientine 26897948, 25369181 MEDNIK syndrome X X AST/ALT (P), Copper (S, U), Ceruloplasmin (S), VLCFA (P) Copper histidine 23423674 Disorders of iron metabolism AST/ALT (P), Glucose (S), Total/direct bilirubin (S), Iron (S), Hereditary hemochromatosis type 1 X HCC Ferritin (S) Phlebotomy 29404472 AST/ALT (P), Glucose (S), Total/direct bilirubin (S), Iron (S), Hemojuvelin deficiency X Ferritin (S) Phlebotomy 12060140 AST/ALT (P), Glucose (S), Total/direct bilirubin (S), Iron (S), Hepcidin deficiency X Ferritin (S) Phlebotomy 12469120 AST/ALT (P), Glucose (S), Total/direct bilirubin (S), Iron (S), Transferrin receptor 2 deficiency X Ferritin (S) Phlebotomy 12060140 AST/ALT (P), Glucose (S), Total/direct bilirubin (S), Iron (S), Ferroportin deficiency X Ferritin (S) Phlebotomy 20691492 Iron (brain, S), copper (S), Ceruloplasmin (S), Ferritin (S), Aceruloplasminemia X Blood count Iron chelation 24002824 Disorders of manganese metabolism SLC30A10 deficiency X X X X X ASAT/ALAT (P), Blood count, Manganese (B) Chelation (EDTA), iron supplementation 22341972, 22341971 DISORDERS OF CARBOHYDRATES Disorders of carbohydrate transport and absorption AST/ALT (P), Glucose (S), Amino acids (U), Urinalysis, Lipid Fanconi-Bickel syndrome X X X HCC panel (S), Oligosaccharide (U), Galactose (RBC) Corn starch, electrolyte replacement 9809815, 28382841 Disorders of galactose metabolism AST/ALT (P), Galactose-1-P (RBC), GALT enzyme activity Classic galactosemia X X X X X HA (RBC) Galactose restriction 14843794, 13914022, 24273939, 12983108 AST/ALT (P), Glucose (S), Amino acids (P), Total/direct Uridine diphosphate galactose-4-epimerase deficiency X X X X bilirubin (S), Oligosaccharide (U) Galactose restriction 10086948, 28247339 Disorders of fructose metabolism AST/ALT (P), Glucose (S), Coagulation factors (P), Total/direct bilirubin (S), Urinalysis, Lipid panel (S), Oligosaccharide (U), Hereditary fructose intolerance X X X X X Sialotransferins (S) Fructose restriction 14304516, 655145, 738900 Disorders of the pentose phosphate pathway and polyol metabolism AST/ALT (P), ALP (S), GGT (S), Glucose (S), Total/direct 24097415, 21119539, 15877206, 23315216, Transaldolase deficiency X X X X X HCC bilirubin (S), Ferritin (S), Polyol (U) 29721915 Glycogen storage diseases Glycogen storage disease type Ib X X X HA, HCC AST/ALT (P), Glucose (S), Blood count Corn starch, G-CSF 12373567, 21481415 AST/ALT (P), CK (P), Glucose (S), Urinalysis, Lactate (P), Lipid Glycogen storage disease type III X X X HA, HCC panel (S), Oligosaccharide (U), Enzyme (DBS, L, F) Corn starch, high-protein diet 17196294, 10914784, 26697579 AST/ALT (P), Coagulation factors (P), Total/direct bilirubin Glycogen storage disease type IV X X X HCC (S), Enzyme (DBS, L, F) Corn starch, liver transplant 13279125 AST/ALT (P), Glucose (S), Urinalysis, Lactate (P), Lipid panel Glycogen storage disease type VI X X X X HA (S) Corn starch 25266922 AST/ALT (P), Glucose (S), Urinalysis, Lactate (P), Lipid panel Glycogen storage disease type IXa X X X (S) Corn starch 25266922 AST/ALT (P), Glucose (S), Urinalysis, Lactate (P), Lipid panel Glycogen storage disease type IXb X X X (S) Corn starch 25266922 AST/ALT (P), Glucose (S), Urinalysis, Lactate (P), Lipid panel Glycogen storage disease type IXc X X X X HA (S) Corn starch 25266922, 28627441 Disorders of gluconeogenesis AST/ALT (P), Glucose (S), Urinalysis, Lactate (P), Lipid panel Glycogen storage disease type I a X X X HA, HCC (S), Uric acid (P) Corn starch 12373567, 21481415 AST/ALT (P), Glucose (S), Amino acids (P), Organic acids (U), Fructose-1,6-bisphosphatase deficiency X X Urinalysis, Lactate (P) 29203193 Cytosolic phosphoenolpyruvate carboxykinase deficiency AST/ALT (P), Glucose (S), Amino acids (P), Organic acids (U) 26971250, 28216384 MITOCHONDRIAL DISORDERS OF ENERGY METABOLISM Disorders of the Krebs cycle AST/ALT (P), Organic acids (U), Acylcarnitines (DBS, P), GTP-specific succinyl-CoA ligase α subunit deficiency X X X Lactate (P) 26475597 Disorders of mitochondrial carriers Cytosolic glycerol-3-phosphate dehydrogenase deficiency X X X X AST/ALT (P), Organic acids (U), Lipid panel (S) 24549054, 22226083, 27368975 Disorders of complex I assembly AST/ALT (P), CK (P), Glucose (S), Amino acids (P), Organic Acyl-CoA dehydrogenase 9 deficiency X X acids (U), Acylcarnitines (DBS, P), Lactate (P) 17564966 Disorders of complex III assembly BCS1L deficiency X X Lactate (P), Iron (S) 11528392, 12215968 Disorders of complex IV assembly and ancillary proteins SCO1 deficiency X X X AST/ALT (P), Lactate (P) 11013136 Disorders of complex V assembly AST/ALT (P), CK (P), Amino acids (P), Organic acids (U), Transmembrane protein 70 deficiency X Lactate (P) 25326274 Disorders of mitochondrial DNA depletion DNA polymerase γ catalytic subunit (POLG1) deficiency X X X X AST/ALT (P), Organic acids (U), Lactate (P) 23419467